The effects of chemotherapeutic agents and radiation on DNA structure and function are being studied in mammalian cell culture by measurements of DNA single-strand breaks and DNA cross-linking. Drug effects in relation to DNA damage and DNA repair are measured by DNA alkaline elution and by ultracentrifugation methods. Agents of current interest include nitrogen mustards, nitrosoureas, bleomycin, and X-ray. Effects on intracellular DNA are being related to survival of colony-forming ability. Interactive effects in combinations of 2 agents are being examined. Studies are planned on the effects of chemotherapeutic agents on DNA strand assembly during DNA replication. Normal and neoplastic cell lines are compared in order to disclose differential cytotoxicity.